Preferential expression of some membrane type matrix metalloproteinase proteins

Membrane type matrix metalloproteinase (MT-MMP) proteins yield clues on endometriosis pathogenesis

Key Points

Highlights:

• Membrane-type matrix metalloproteinase (MT-MMP) proteins are mainly found in endometrial epithelial glandular and luminal cells without cycle dependency.

Importance:

• This is a pioneering study analyzing Membrane-type matrix metalloproteinase proteins in healthy patients' endometrium versus endometrium of patients with endometriosis, endometrium with adenomyosis, also comparing with adenomyosis, ovarian endometriosis, peritoneal endometriosis, and deep infiltrating endometriosis.

What’s done here:

• MT-MMPs namely MT2-MMP (MMP15) and MT3-MMP (MMP16) were analyzed in eutopic endometrium with and without endometriosis and with and without adenomyosis.
• Ectopic endometrium of deep infiltrating endometriosis, peritoneal endometriosis, and ovarian endometriosis was also analyzed.
• The protein analysis was performed by immunohistochemistry.

Key results:

• Both MT2-MMP (MMP15) and MT3-MMP (MMP16) proteins were found to be localized in endometrial epithelial glandular and luminal cells in the eutopic endometrium
• There was no difference in expression during the menstrual cycle.
• Both proteins were reduced and showed a heterogeneous abundance in three distinct endometriosis entities but nearly remained stable in adenomyosis.
• This may be a clue that endometriosis and adenomyosis do not share a common pathogenesis and that most of the differences in eutopic endometriotic implants occur after but not before implantation.

Lay Summary

Dr. Maoga and associates from academic institutions located in Germany and Kenya have published their findings on the immunohistochemical expression of MT-MMP proteins, namely MT2-MMP (MMP15) and MT3-MMP (MMP16) in the eutopic endometrium of healthy and endometriotic patients; and also in adenomyosis and different types of endometriosis, in the journal named Diagnostics.

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases capable of degrading extracellular matrix and are involved in different physiological processes like cell proliferation, differentiation, angiogenesis, apoptosis, and cell migration. These proteins are mainly found in endometrial epithelial glandular and luminal cells without cycle dependency. 

Preferential expression of both proteins was observed in the glandular and luminal epithelial cells of the eutopic endometrium of patients with and without endometriosis and was reduced and heterogeneous abundance in three distinct endometriotic entities but nearly remained stable in adenomyosis.

The similar expression levels of MT2-MMP and MT3-MMP in eutopic endometrium in patients with and without endometriosis, when compared to the deterred expression in ectopic endometrium, yields that alterations occur after and not before endometrial implantation due to distinct interactions with the different environments. The differential protein expression of MT2/3-MMP in adenomyosis compared to endometriosis is also suggestive of a different pathogenesis pathway for the two diseases.

The authors concluded that the results of the study suggest that the endometrial glands should be the main source of adenomyotic glands, and most of the differences among eutopic endometriotic implants occur after and not before implantation, possibly due to the distinct interactions of the endometrial implants with different microenvironments. Also, endometriosis and adenomyosis may not share a common pathogenesis and further research is necessary to understand the functional role of these proteins.

Research Source: https://pubmed.ncbi.nlm.nih.gov/35453827/